title: Intraclonal competition inhibits the formation of high-affinity antibody-secreting cells.
abstract: Protective immunity requires a diverse, polyclonal B cell repertoire. We demonstrate that affinity maturation of the humoral response to a hapten is impaired when preexisting clonally restricted cells recognizing the hapten are dominant in the B cell repertoire. B1-8i(+/-) mice, which feature a high frequency of B cells with nitrophenyl (NP)-binding specificity, respond to NP-haptenated proteins with the production of NP-specific Abs, but affinity maturation is impaired due to insufficient generation of high-affinity Ab-producing cells. We manipulated the frequency of NP-specific B cells by adoptive transfer of B1-8 B cells into naive, wild-type recipients. Remarkably, when 10(4) B1-8 B cells were transferred, these cells supported efficient affinity maturation and plasma cell differentiation. In contrast, when 10(6) B1-8 cells were transferred, affinity maturation did not occur. These data indicate that restricting the frequency of clonally related B cells is required to support affinity maturation.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Thuc-vy L
authors.initials: TV
authors.lastname: Le
authors.forename: Tea Hyun
authors.initials: TH
authors.lastname: Kim
authors.forename: David D
authors.initials: DD
authors.lastname: Chaplin
mesh_terms: D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D002999:Clone Cells; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009596:Nitrophenols / Q000276:immunology / Q000378:metabolism; D010648:Phenylacetates / Q000276:immunology / Q000378:metabolism; D010798:Phycocyanin / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin
chemical_list: D009596:Nitrophenols; D010648:Phenylacetates; D011947:Receptors, Antigen, B-Cell; C002497:allophycocyanin; C026242:4-hydroxy-5-nitrophenyl acetic acid; D010798:Phycocyanin